WO1996014922A1 - Hydrophilic film and process for producing the same - Google Patents

Abstract

A hydrophilic film comprising a hydrophobic aromatic polymer film and, adsorbed thereto irreversibly, a hydrophilic cellulose derivative with a number-average molecular weight of 2,000 to 8,000. As the film is remarkably reduced in exudates, it is usable also in the fields of medicines and electronics where exudates must be avoided.

Description

 Field damage Hydrophilic membrane and method for producing the same

 The present invention is directed to a hydrophilic membrane obtained by hydrophilizing an aromatic polymer-based hydrophobic 胰 and a method for producing the same. It can be effectively used for 過 perfusion membrane, medical membrane, etc. Background art

 A method for hydrophilizing a hydrophobic membrane in which a hydrophobic membrane is impregnated with a hydrophilic polymer solution and then the solvent is dried to attach a hydrophilic polymer has been known for a long time, and all known hydrophilic polymers are wiped. S "It was enough.

 It is also well known that a cellulose derivative is used as a hydrophilic polymer. For example, Japanese Patent Publication No. Sho 56-16187 exemplifies methylcellulose, ethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose. Hydroxypropyl cellulose having a molecular weight of 1000 or more is used.

In the conventional technology, emphasis has been placed on making the hydrophobic membrane a hydrophilic membrane or insolubilizing the hydrophilic polymer, and a technology to prevent even the elution of even a minute amount of the hydrophilic polymer has been studied. I didn't. However, in fields such as medical or electronics, even very small microvesicles eluted from 胰 can be a serious question, and such traces of eluate may be prohibited. However, there are many cases where conventional technology cannot sufficiently meet this demand. A cellulose conductor used as a hydrophilic polymer is produced by chemically modifying powdered or flaky cellulose. Therefore, some cellulose derivatives do not completely dissolve in a solvent, remain in a dispersed state, and remain cellulose that has not been sufficiently chemically modified. When a solution containing such a cellulose derivative is impregnated into a hydrophobic membrane, the portion that is not completely dissolved not only closes the pores of the membrane, but also retains the hydrophobic membrane in a molecular state after drying. Since it has not irreversibly adsorbed on the surface (meaning that at least the molecule once adsorbed is redissolved in water and does not escape from the hydrophobic K), it elutes under severe conditions such as autoclave sterilization. May come.

 The object of the present invention is not only to convert hydrophobic 腠 into a hydrophilic membrane, but also to make it possible to use eluate sufficiently in fields where a small amount of eluate is prohibited, such as medical or electronics. An object of the present invention is to provide a hydrophilic film with a minimum amount. Disclosure of the invention

 A first feature of the present invention is that a hydrophilic cellulose derivative having a number average molecular weight of 2000 to 800 is irreversibly adsorbed on an aromatic polymer-based hydrophobic membrane. Film.

 A second aspect of the present invention is a hydrophilicity characterized by impregnating a hydrophobic membrane with a solution of a hydrophilic cell opening source-conductor having a number average molecular weight of 2000 to 800 and then washing the membrane. This is a method for producing a film. BEST MODE FOR CARRYING OUT THE INVENTION

The present invention is to produce a hydrophilic が with very few eluted substances by irreversibly adsorbing a hydrophilic cell derivative, which is not completely dissolved in a solvent, by preliminarily fractionating and removing the same, onto a hydrophobic membrane. But usually cellulose As a method for removing the insoluble portion from the conductor, it is conceivable to use a hydrophilic cellulose derivative solution. However, unexpectedly, the concentration of the insoluble portion is too fast, and the insoluble portion having a small pore size of the filter is too high. It is not an effective method because it remains.

 Therefore, in the present invention, the insoluble portion is removed by fractionation using a poor solvent, which is usually used for molecular weight fractionation (hereinafter, referred to as fractionation method). According to this method, the insoluble portion precipitates as a large aggregate together with the high molecular weight component, so that it can be reliably removed.

 As the hydrophilic cellulose derivative, methylcellulose, carboxymethylcellulose, low S-substituted hydrid D xybu pill cellulose, and hydroquinpropylmethylcellulose are preferable, and these are used alone or in combination of two or more. These hydrophilic cellulose derivatives are easy to handle because they are dissolved in water or an aqueous alkali solution. The solvent used to separate the insoluble portion from the cell D-semiconductor is not particularly limited. For example, water, ethanol, an aqueous ethanol solution, an aqueous ethanol solution, or the like is preferably used. be able to. Furthermore, as is well known, the molecular weight of the fraction can be adjusted by changing the solubility of the fractionation solvent. Large agglomerates containing insoluble parts precipitated by fractionation can be passed through paper, etc., but in the case of spontaneous precipitation, components that do not contain insoluble parts can be obtained only by collecting the supernatant solution. be able to.

The commonly available cellulose (number average molecule of conductor) is about 10,000 to 300,000 (for example, see the section of this pharmacopoeia, hydroxybutyrvir methylcellulose). As the molecular weight increases, the proportion of the insoluble portion is also cultivated. Therefore, it is preferable that the raw material before separation has as small a molecular weight as possible. When the insoluble portion is separated from such waste material by the method described above, A cellulose bead having an average molecular weight of S = 2000 to 800 is obtained.

 The hydrophobic polymer used in the present invention comprises an aromatic polymer, for example, an aromatic polyester, an aromatic polyester, an aromatic boride, an aromatic polyimid, an aromatic polysulfone, or a mixture of two or more aromatic polymers. However, aromatic polysulfones such as polyethersulfone and polyallylethersulfone are particularly preferable because they have excellent basic properties such as chemical resistance, mechanical strength, heat resistance, and permeability.

 In the above-mentioned Japanese Patent Application Laid-Open No. Sho 62-176658, the hydroxybutyryl group is an effective hydrophobic binding residue to polysulfone, and in order to increase this number, the hydroxybutyrate having an average molecular weight of 10,000 or more is required. Although it is stated that oral pill cellulose must be used, the present inventors have found that methylcellulose ゃ hydroxybutyrate has a hydroxyl group content of about 1/10 that of hydroquinpropylcellulose. Since pillmethylcellulose and low-substituted hydroxypropylcellulose adsorb more strongly than hydroxydipropylcellulose, the hydrophobic binding group for aromatic residues is the glucose residue itself, which is the cellulose skeleton. Hydroxypropyl group gives hydrophilicity like methoxy group, but prevents hydrophobic bond to polysulfone. Considered.

 Therefore, in the present invention, a cellulose derivative having an amount of about 40% or less for generating a strong irreversible bond and about 10% or more for imparting hydrophilicity is used in the present invention. Is preferred. By using such a cell α-source derivative, even if the molecular weight is less than 10,000, it can be strongly irreversibly adsorbed to polysulfone and impart hydrophilicity. However, if the molecular weight is less than 2000, the cohesive force still decreases.

The present invention uses a low molecular weight cellulose derivative V, so that it can be effectively used for a membrane having a pore size of about 0.01 μm or more without lowering the ffi rate. it can. K may be either a hollow fiber or a film.

 The above-mentioned solvent is used as a solvent for irreversibly adsorbing the solution of the cell-mouthed derivative in the hydrophobic layer ', and the above-mentioned solvent is used. In particular, water or an alkaline aqueous solution is preferably used. A small amount of alcohol such as ethanol may be added to these solutions for quick inclusion. The g-degree of the cell c 锈 conductor is approximately 50 to 100 O ppm. If it is less than 50 ppm, it may not be adsorbed on the entire film surface, and if it exceeds 100 ppm, the adsorption is not promoted, so it is not significant. In the above-mentioned Japanese Patent Application Laid-Open No. 62-176658, a hydrophobic film is brought into contact with a solution of a cellulose conductor for several hours or more. In the present invention, however, a cellulose carrier having a low molecular weight and a large binding force is used. Since it is used, the adsorption speed is high, and this contact time of about 10 minutes or more and 2 hours or less is sufficient.

 In the case where the hydrophobic membrane is included, if the hydrophobic membrane is previously wetted with water, it may be simply immersed in a solution of a cellulose derivative, and if it is dry, it is forcibly pressed. Since the solubility of the cellulose derivative in water is reduced above about 60 "C, the temperature of the solution is preferably from room temperature to 50.

 After the cellulose conductor is adsorbed on the entire surface of the hydrophobic membrane, the unnecessary cellulose derivative solution is washed with the same solvent in the chambers 溫 to 50 so that the cellulose derivative adhered in an unstable state is not generated. Remove. If the solvent is an aqueous solution, wash it further. It can be dried if necessary. The dried film is hydrophilic enough to be naturally wetted by water.

Whether the cellulose derivative is adsorbed on the entire surface of the hydrophobic membrane and becomes hydrophilic (腠) can be determined by the bleeding point (for example, see JISK 382) or the air diffusion flow rate (for example, JISK 383). You can check. Whether the cellulose derivative is blocking the pores of the hydrophobic membrane is determined by the flow rate of water (for example, JISK 3831). You can check. The hydrophilicity of the present invention is completely hydrophilic, and the pores are not closed by the cellulose conductor.

 The eluate from the obtained hydrophilic membrane can be confirmed by, for example, the Japanese Pharmacopoeia, the test method for plastic containers for orbital fluid, or the measurement of total organic carbon (TOC) S in the eluate. On the other hand, the hydrophilic membrane of the present invention has a very small amount of eluate.

 Hereinafter, the present invention will be described in more detail with reference to Experimental Examples, Examples, and Comparative Examples, but the present invention is not limited thereto.

Experimental example 1

 (1) Fractionation of low-molecular-weight hydroxypropylmethylcellulose Hydroxypropylmethylcellulose from Ichisaka with a number-average molecular weight of about 11 000 and a methoxy group and a hydroxyl group of 29 kappa, respectively. Hereafter, it is called HPMC). : Dispersed and left overnight. The clear supernatant was separated and HPMC having an average molecular weight of 2500 was collected. Similarly, HPMC having an average molecular weight of 7,500 was fractionated using ethanol containing a small amount of water for the separation.

 (2) Test for confirming the effect of removing insoluble parts

 A 100 Oppm aqueous solution of the above three types of HPMC was passed through a filter having a pore size of 0.04 μm. The feed pressure of the raw material HPMC aqueous solution increased more than twice within 1 minute, but the dependent pressure of the other two aqueous solutions hardly increased even after 1 hour, confirming that the insoluble portion was removed. Was.

Example 1

 (1) Preparation of hydrophilic hollow fiber

A solution of 20 parts by weight of poly (aryl ether sulfone) (T-3, P-3500) and 80 parts by weight of dimethyl sulfokind is used. Propylene glycol containing a small amount of water while holding at C Extruded into the air from the double tubular nozzle together with the aqueous solution, about below the nozzle

After infiltrating into warm water of 10 cm, it was wound and hollow fibers having a pore diameter of about 0.02 wm and inner and outer diameters of 200 and 260 jum, respectively, were prepared. A bundle of 800 cm of this hollow fiber having a length of about 30 cm was washed with hot water until the residual amount of dimethyl sulfoxide became about 1 ppm.

 This hollow fiber bundle was impregnated with a 500 ρρηη aqueous solution of HPMC having an average molecular fi of 250, while showering at 40 for 1 hour, and then immediately showered with 50 • C water for 1 hour. Then, the aqueous solution of HPMC was washed away. The hollow fiber bundle was dried at 90 ° C.

 (2) Measurement of eluate from hydrophilic hollow fiber membrane

 The eluate of the hydrophilic hollow fiber obtained in Example 1 above was subjected to the method of the Japanese Pharmacopoeia, plastic container for orifice II, and the permanganate power consumption of the eluate was measured. , 0.4 ppm, which was within the standard. In addition, the concentration was 310 (the concentration was 301). These values indicate that the amount of eluted substances was extremely small.

 (3) Measurement of excess flow

 The flow rate of the hydrophilic hollow fiber membrane obtained in Example 1 was measured by the following method. That is, a module having an effective length of about 18 cm in which both ends of a hydrophilic hollow fiber were bundled and fixed with a urethane resin by a known method was prepared. The flow rate of water in this hollow fiber membrane module is almost the same as that obtained by flowing an aqueous ethanol solution through a module consisting of hydrophobic hollow fibers before hydrophilization treatment and then measuring the water flow rate. It was confirmed that the pores of the hydrophobic membrane hydrophilized by HPMC were not closed.

 (4) Hydrophilicity integrity test

When the above-mentioned hydrophilic hollow fiber module with water flow is pressurized from the outside of the hollow fiber with air of 300 kPa, the dispersion flow rate is 15 ml / min or less. Thus, it was determined that HPMC was adsorbed on the entire surface of the hollow fiber.

Example 2

 When the same evaluation as in Example 1 was performed using HPMC having an average molecular weight of 7,500, the same results as in Example 1 were obtained.

Comparative Example 1

 When the same evaluation as in Example 1 was performed using the raw material HPMC as it was, the eluate passed 1.6 ppra of manganese and potassium, which was out of the standard. The TOC was 1 Oppm.

Example 3

 (1) Preparation of hydrophilic hollow fiber membrane

 While maintaining a solution consisting of 13 parts by weight of polysulfone, 25.5 parts by weight of propylene glycol and 61.5 parts by weight of N-methyl-2-virolidone at 85, 70 parts by weight of N-methyl-2-pyrrolidone? The mixture was extruded from the double tubular nozzle together with the 6 aqueous solution, and hollow fibers having a pore diameter of 0.2 μm, inner and outer diameters of S 40 μm and 440 m were prepared in the same manner as in Example 1. A bundle of 2800 hollow fibers having a length of about 30 cm was washed with hot water until the residual amount of the solvent became 5 ppm or less.

 This hollow fiber was hydrophilized with HPMC in the same manner as in Example 1.

 (2) Evaluation of eluate, flow rate and completeness of hydrophilicity

 When these were evaluated in the same manner as in Example 1, almost the same results as in Example 1 were obtained.

Experimental example 2

Confirmation test for irreversible adsorption

After the hydrophilic hollow fiber membranes obtained in Examples 1, 2 and 3 were dipped in high-pressure hot water at 135 for 1 hour and dried, the amount of overflow was determined in the same manner as in Example 1. Was measured and the integrity test of hydrophilicity was performed. As a result, it was confirmed that HPMC did not female escape from the hollow fiber belly by this treatment.

Comparative Example 2

 A hollow fiber was prepared in the same manner as in Example 3 except that a 50 ppm aqueous solution of pill cellulose having an open mouth with a hydroxyl group having an average molecular weight of about 1100 and a hydroxyl group having a hydroxyl group of 62% was used. . The obtained hollow fiber not only had a reduced excess flow rate, but also had a large spreading flow rate that was unmeasurable, and it was judged that the quinoline propylcell CIase was not adsorbed on the entire surface of the polysulfone. Industrial applicability

 The hydrophilic membrane of the present invention can be used in applications where minute eluting substances are prohibited since the amount of eluting substances is extremely small. In addition, the production method of the present invention has a feature that, since the molecular weight of the hydrophilic cellulose derivative is small, even a hydrophobic membrane having a relatively small pore diameter can be made hydrophilic without closing the pore.

Claims

The scope of the claims 1. A hydrophilic membrane characterized by the fact that a hydrophilic cellulose derivative having a number average molecular weight of 2000 to 800 is irreversibly adsorbed on an aromatic polymer-based hydrophobic membrane.  2. The hydrophilic membrane according to claim 1, wherein the aromatic polymer-based hydrophobic membrane is an aromatic polysulfone-based membrane.  3. The hydrophilic membrane according to claim 1 or 2, wherein the hydrophilic cell π-source derivative is hydroxymethyl pyrmethylcellulose.  4. A method for producing hydrophilic erythr, which comprises clarifying a solution of a hydrophilic cellulose derivative having a number average molecular weight of 2000 to 800 to a hydrophobic layer, followed by washing.